Semiempirical QM/MM calculations reveal a step-wise proton transfer and an unusual thiolate pocket in the mechanism of the unique arylpropionate racemase AMDase G74C

F. Busch, J. Enoki, N. Hülsemann, Kenji Miyamoto, M. Bocola, R. Kourist

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Abstract

The mechanism of the unique arylpropionate racemase AMDase G74C was investigated by a QM/MM approach. Molecular dynamics simulations showed that the mechanism is initiated by a deprotonation of the catalytic cysteine. The simulations revealed two thiolate pockets. While the first plays a role in the natural decarboxylative activity of AMDase, the second stabilizes the artificially introduced thiolate group of C74. The presence of the two structural motifs is a prerequisite for the promiscuous racemization reaction of AMDase G74C. QM/MM simulations show that the deprotonation and reprotonation proceed in a stepwise fashion, in which a planar enedionate intermediate is stabilized by a delocalized π-electron system on a vinylic or aromatic substituent of the substrate. The artificial racemase is thus a typical case of substrate-assisted catalysis.

Original languageEnglish
Pages (from-to)4937-4944
Number of pages8
JournalCatalysis Science and Technology
Volume6
Issue number13
DOIs
Publication statusPublished - 2016

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Racemases and Epimerases
Deprotonation
Proton transfer
Substrates
Catalysis
Cysteine
Molecular dynamics
Electrons
Computer simulation

ASJC Scopus subject areas

  • Catalysis

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Semiempirical QM/MM calculations reveal a step-wise proton transfer and an unusual thiolate pocket in the mechanism of the unique arylpropionate racemase AMDase G74C. / Busch, F.; Enoki, J.; Hülsemann, N.; Miyamoto, Kenji; Bocola, M.; Kourist, R.

In: Catalysis Science and Technology, Vol. 6, No. 13, 2016, p. 4937-4944.

Research output: Contribution to journalArticle

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